The cause and pathogenesis of injury in most chronic degenerative diseases of man are unclear. At present, there are several animal models in which viral infection and the pathogenesis of resultant tissue injury associated with persistent virus infection can be studied. With one model, infection of mice with lymphocytic choriomeningitis (LCM) virus, we now understand that: lifelong viral persistence follows either neonatal or in utero infection, along with equally sustained host immune responses against the virus and that interaction of the virus with products of the antiviral immune response is the cause for most of the tissue injuries seen. The objective of this proposal continues to be the study of how virus persists in the face of an antiviral immune response and to investigate the fate of membrane bound viral antigens and fluid phase viral antigens after they have interreacted with antiviral antibodies alone, antiviral antibodies and complement, sensitized lymphoid cells and/or macrophages. Specific focus is on the origin and fate of virus specific antigen-antiviral antibodies in immune complexes. Other studies are directed towards determining the specific viral antigens expressed on the surfaces of infected cells that are recognized by antibody and complement or sensitized T lymphocytes, macrophages and natural killer cells. We are also interested in learning how the virus is assembled in infected cells.